The role of microRNAs in cardiovascular disease.

Cardiovascular disease has become the main factor of death and birth defects in the world. There are some therapeutic structures and drugs for curative and palliative therapy of the disease, but to the aim of accessing reliable therapy or to postpone onset of disease, especially for individuals with heritable coronary artery disease in their pedigree Genetic engineering technologies are making advances in the field by identifying oligonucleotides with higher potencies which can be easily targeted against almost any gene, particularly interfering RNA (RNAi). Recently, the focus of RNAi approaches has encompassed the use of synthetic sequences to mimic or silence endogenous microRNAs (miRNAs) that are abruptly dysregulated following cardiovascular diseases. In this review, we summarize the role of miRNAs in heart development and vascular system as two main factors of birth defects and adult morbidity and mortality and miRNAS as new therapeutic agents.

level, and pulse rate with blood pressure phenotypes as environmental factors and all the traits have shown a significant association (4,5 inheritance, the strategy used to identify their genes of predisposition is usually not based on family studies but on a radically different approach called "genetic association" analysis (6). Also, in the case of complex diseases such as myocardial infarction (MI), linkage analysis is compounded by genetic heterogeneity of this disease and many other factors, including incomplete penetrance of diseasecausing genes interaction with environmental factors, the high prevalence of the disease-causing allele in the population, and late onset of disease (7). According to researches based on Metaanalysis technique published on 2011, specific genetic loci were introduced to be related with cardiovascular disease and more specifically with MI. Expression changes in some of them cause increasing risk of MI (8,9).
Regarding these loci as important genetic risk factors for the disease, endogenous micro RNAs (miRNAs) can be considered as factors Recently, the focus of interfering RNA (RNAi) approaches has encompassed the use of synthetic sequences to mimic or silence endogenous miRNAs that are abruptly dysregulated following cardiovascular diseases. The implications of miRNAs in the pathological process of the cardiovascular system have recently been recognized, and research on miRNAs in relation to cardiovascular disease has now become a rapidly evolving field (10).

Biology of miRNA
Epigenetic control mechanisms including DNA methylation, histone modification, and non coding RNAs as well as differential RNA splicing, play a key role in the regulation of tissue homeostasis and disease development and enable the cell to respond quickly to environmental changes (11,12). Noncoding RNAs are functional RNA molecules that belong to several groups and are involved in many cellular processes. miRNAs Each miRNA duplex is formed by a guide strand and a passenger strand. An enzyme within the RISC, the endonuclease Argonaute 2 (Ago 2) catalyzes the unwinding of the miRNA duplex.
Once unwound, the guide strand is incorporated into the RISC, while the passenger strand is released. RISC uses the guide strand to find the mRNA that has a complementary sequence leading to the endonucleolytic cleavage of the target miRNA (17).

miRNAs in Cardiovascular Disease
Recent studies have shown that miRNAs play an essential role in some biological processes such as cell proliferation or cell differentiation, and apoptosis. Also, they are associated with important diseases including cancer and cardiovascular diseases (18)(19)(20). Caré et al, found that the expression of miR-133, which was transcribed together with miR-1 as a bicistronic cluster, was decreased in the left ventricle of the above mentioned three hypertrophic models (42). Mice lacking either miR-133a-1 or miR-133a-2 that survive to adult, suffer from dilated cardiomyopathy and succumb to heart failure.
These experiments prove the important role of miRNAs for the development of the organ. The heart as a particularly informative model for such organ patterning, has numerous transcriptional networks that establish chamber-specific gene expression and function (32,43).

miRNAs as therapeutic agents
There are some therapeutic structures and drugs for curative and palliative therapy of the disease, but to the aim of accessing reliable therapy or to postpone the onset of disease, especially for people with heritable coronary artery disease in their pedigree. Genetic engineering technologies are making advances in the field by continually identifying oligonucleotides with higher potencies, particularly interfering RNA (miRNA); more effective cellular targets, typically in signaling pathways; and delivery approaches with the next generation of drug platforms (64). The presence of cell-free miRNAs has been detected in a range of body fluids. The miRNA content of plasma/serum in particular has been proposed as a potential source of novel biomarkers for a number of diseases (65).
So, there are many miRNAs which participate in cardiac related diseases and also their changes can be considered as a biomarker for the disease (27)(28)(29)(30). The use of miRNAs as biomarkers has greatly increased as a result of the discovery that they are present in the circulating blood. A number of groups have shown that miRNAs can be detected in human serum or plasma, where they are thought to be protected from degradation by being encapsulated in microvesicles or exosomes and/or are bound by RNA-binding proteins such as Ago2 and nucleophosmin (19,30,65). These findings can be considered as new strategies for cardiovascular disease therapies. Among these miRNAs, some of them were recognized as the key elements in processing of CAD such as miR-126, miR-21, miR-143 and miR-145. Thus, the next researches should be focused on the accuracy of the miRNAs as biomarker in CAD.

Conflict of interest:
Non declared.